In this proposed career development award, I aim to build upon the work of my previous career award. Funded by that award, I examined the relation between prenatal insults and adult schizophrenia spectrum disorders (SSD) in three birth cohorts, and identified several novel associations. In the current award I will extend this work in several ways. First, I will investigate whether early developmental exposures are associated with an increased risk of SSD. Second, I will assess whether early developmental exposures are associated with structural and functional brain abnormalities in patients with SSD. Third, I will examine the relation of genetic vulnerability to early developmental insult in SSD. To achieve this objective I will receive further training in neuroimaging, genetic epidemiology, and other research areas from distinguished experts. This will include direct supervision, formal coursework, readings, and seminars. The research arm of the award will utilize prospectively acquired data on prenatal viral infection and other early developmental insults in two birth cohorts in which I have completed follow-up studies for schizophrenia. Unlike previous studies, serologic analysis will be used to document prenatal viral exposures and cytokine elevations in relation to the risk of schizophrenia. Subjects in these cohorts will receive neuroimaging assessments, including volumetric magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H MRS), and a comprehensive neuropsychological test battery. A summary measure of early developmental insult will then be examined in relation to specific structural and functional brain abnormalities detected by the above methodologies. In the genetics section of the proposal, I will test models of gene-environment interaction. [unreadable] [unreadable]